Sera of patients with rheumatoid arthritis contain antibodies to recombinant human T-lymphotrophic virus type I/II envelope glycoprotein p21.

A possible retroviral etiology for rheumatoid arthritis (RA) has been raised by results of recent studies. Therefore, we examined sera of patients with RA, including those with coexisting Felty's syndrome or leukemia of large granular lymphocytes, for the presence of antibodies to retroviral proteins of human T-lymphotrophic virus type I and type II (HTLV-I/II). Reactivity to recombinant HTLV-I envelope protein rgp21 alone was the primary pattern observed. Twenty-five percent of RA sera, 28% of Felty's syndrome sera, and 30% of large granular lymphocyte leukemia/RA sera reacted with rgp21, each significantly more than the 8% of normal sera (P less than 0.01). Removing rheumatoid factor did not abolish reactivity with rgp21 in any of six RA sera tested. Immunoreactivity to the authentic viral protein was confirmed by using purified rgp21 that was cleaved by CNBr to remove the bacterial fusion peptide, or by blocking sera with a synthetic peptide corresponding to the fusion peptide. Only one serum, from a patient with RA, showed definite evidence for prior infection with prototypic HTLV-II. These data indicate that 25% of RA sera have IgG antibodies to recombinant HTLV-I envelope protein rgp21, which is highly homologous to envelope protein gp21 of HTLV-II. These findings provide potentially novel clues regarding the pathogenesis of RA.

A denaturant-insoluble form of tyrosine hydroxylase in PC12 pheochromocytoma cells.

A 6M urea-insoluble form of tyrosine hydroxylase (THi) was detected in PC12 pheochromocytoma cells by western blotting immunodetection methods, and the characteristics and mechanisms of formation of this insoluble species were investigated. THi accounts for about 4% of the immunodetectable tyrosine hydroxylase in exponentially dividing pheochromocytoma cells. It is unlikely that a subpopulation of dead or dying cells is the source of THi since essentially no changes in THi levels were detected when cell death was intentionally increased. To measure the kinetics of formation of cellular THi, exponentially dividing cells were metabolically labeled first with [3H]leucine and then with [14C]leucine, and though both 3H and 14C were incorporated into soluble tyrosine hydroxylase, the near absence of 14C in THi demonstrated that a lag period of at least a day exists between biosynthesis of tyrosine hydroxylase and the accumulation of measurable THi. The cellular accumulation of THi can evidently be regulated by the cell, since upon nerve growth factor (NGF) treatment of cells the total content of tyrosine hydroxylase increased and the content of THi decreased to yield, overall, a fivefold lower proportion of THi after 4 days. A large increase in urea-insoluble enzyme was found upon sublethal exposure of cells to ferrous ion and hydrogen peroxide, indicating that oxidative damage via metal-ion-catalyzed formation of hydroxide free radical can yield an enzyme that is similar in its insolubility to THi.